In cancer diagnosis, it is important from the viewpoint of QOL to minimize pain and invasion in patients. Another key demand is to prevent healthy people from being unnecessarily disadvantaged by suspicion of having cancer. In recent years, minimally-invasive diagnostic imaging technology has advanced, and based on the fact that cancer cells take up a large amount of glucose, positron emission tomography (hereinafter referred to as “PET”) using a 18F-labeled glucose analog 18F-fluorodeoxyglucose (18F-FDG) is widely used. However, FDG has a disadvantage in that its uptake occurs in lesions other than cancer, such as inflammatory sites, leading to false positive results. Particularly, FDG uptake has been shown in normal tissues of the brain and inflammatory sites, and for this reason, the application of FDG is limited. Furthermore, the use of FDG in diabetic patients, who have difficulty in controlling their blood sugar levels, is also limited.
The present inventors previously discovered a novel amino acid transporter designated LAT1 (L-type amino acid transporter 1), which is responsible for amino acid uptake in cancer cells (Non Patent Literature 1). LAT1 is absent in normal cells in most tissues, but malignant transformation induces the expression of LAT1. Therefore, LAT1 can be used as a molecular marker of cancer diagnosis. In addition, the present inventors found an amino acid derivative that inhibits the cancer cell-specifically expressed amino acid transporter LAT1 and thereby suppresses cancer cell proliferation, and based on the findings, received a patent therefor (Patent Literature 1).
Furthermore, the present inventors conducted PET scans in lung cancer patients using 18F-labeled fluoro-α-methyltyrosine (hereinafter referred to as “FAMT”). FAMT is known to be intracellularly transported more dominantly via the cancer cell-specific amino acid transporter LAT1 than via an amino acid transporter designated LAT2 (L-type amino acid transporter 2), which is expressed in normal cells. The PET results showed that FAMT accumulated in cancer similarly to FDG and had a potential application for cancer diagnosis (Non Patent Literature 2). FAMT does not accumulate in inflammatory lesions and is highly selective for cancer, and therefore is a highly versatile PET probe that is applicable even to brain tumor, to which FDG is inapplicable.
However, the accumulation of FAMT is slightly less intense than that of FDG, and there is room for further improvement. Another problem is that the labeling of FAMT cannot be carried out with automated synthesizers commonly used in PET-installed institutions. Therefore, compounds for PET probes that can be labeled using automated synthesizers in the same manner as FDG are desired to be developed.